David Garmire

A Global Clustering Algorithm to Identify Long Intergenic Non-Coding RNA - with Applications in Mouse Macrophages

Identification of diffuse signals from the chromatin immunoprecipitation and high-throughput massively parallel sequencing (ChIP-Seq) technology poses significant computational challenges, and there are few methods currently available. We present a novel global clustering approach to enrich diffuse CHIP-Seq signals of RNA polymerase II and histone 3 lysine 4 trimethylation (H3K4Me3) and apply it to identify putative long intergenic non-coding RNAs (lincRNAs) in macrophage cells. Our global clustering method compares favorably to the local clustering method SICER that was also designed to identify diffuse CHIP-Seq signals. The validity of the algorithm is confirmed at several levels. First, 8 out of a total of 11 selected putative lincRNA regions in primary macrophages respond to lipopolysaccharides (LPS) treatment as predicted by our computational method. Second, the genes nearest to lincRNAs are enriched with biological functions related to metabolic processes under resting conditions but with developmental and immune-related functions under LPS treatment. Third, the putative lincRNAs have conserved promoters, modestly conserved exons, and expected secondary structures by prediction. Last, they are enriched with motifs of transcription factors such as PU.1 and AP.1, previously shown to be important lineage determining factors in macrophages, and 83% of them overlap with distal enhancers markers. In summary, GCLS based on RNA polymerase II and H3K4Me3 CHIP-Seq method can effectively detect putative lincRNAs that exhibit expected characteristics, as exemplified by macrophages in the study.

Diamagnetically Levitated MEMS Accelerometers

We introduce the theory and a proof-of-concept design for MEMS-based, diamagnetically-levitated accelerometers. The theory includes an equation for determining the diamagnetic force above a checkerboard configuration of magnets. We demonstrate both electronic probing and a rapid MEMS-based interferometer technique for position sensing of the proof mass. Through a proof-of-concept design, we show electrostatic-measurement sensitivity achieving 34 mug at a 0.1 V sense signal and interferometer-measurement sensitivity achieving 6 mug for in-plane vibrations at 5 Hz. We conclude by outlining batch-fabrication steps to produce levitated accelerometers.

Simple Fabrication Process for Self-Aligned, High-Performance Microscanners— Demonstrated Use to Generate a 2-D Ablation Pattern

A new, straightforward, complementary metal-oxide-semiconductor (CMOS)-compatible, three-mask process is used to fabricate high-performance torsional microscanners driven by self-aligned, vertically offset comb drives. Both the moving and fixed combs are defined using the same photolithography mask and fabricated in the same device layer, a process allowing the minimum gap between comb fingers to be as small as twice the alignment accuracy of the photolithography process. Our fabricated microscanners have torsional resonant frequencies between 58 Hz and 24 kHz and maximum optical-scanning angles between 8deg and 48deg with actuation voltages ranging from 14.1 to 67.2 Vac-rms. The yields on two separate fabrication runs have been better than 70%. To demonstrate an application for these scanners, we used them to generate laser-ablation patterns suitable for ocular cornea surgery. We assembled a 2-D scanning system by orienting two identical microscanners at right angles to one another. When driven by two 90deg out-of-phase 6.01-kHz sine waves, the cross-coupled scanners produce circular patterns having radii fixed by the amplitude of the driving voltage. Then, we emulated a small pattern from the surface topography found on a U.S. Roosevelt dime and built up an ablation pattern that compares favorably with similar emulations reported by earlier researchers who used larger, more complicated ablation systems

3-axes MEMS Hall-effect sensor

A 3-axes Hall-effect sensor was fabricated using the PolyMUMPs process based on the MEMS design software, Coventorware. We document the fabrication of this MEMS device and report its preliminary performance based on comparisons to a laboratory Gauss meter.

mirMark: a site-level and UTR-level classifier for miRNA target prediction

MiRNAs play important roles in many diseases including cancers. However computational prediction of miRNA target genes is challenging and the accuracies of existing methods remain poor. We report mirMark, a new machine learning-based method of miRNA target prediction at the site and UTR levels. This method uses experimentally verified miRNA targets from miRecords and mirTarBase as training sets and considers over 700 features. By combining Correlation-based Feature Selection with a variety of statistical or machine learning methods for the site- and UTR-level classifiers, mirMark significantly improves the overall predictive performance compared to existing publicly available methods. MirMark is available from https://github.com/lanagarmire/MirMark.

A simple process to fabricate self-aligned, high-performance torsional microscanners; demonstrated use in a two-dimensional scanner

CMOS-compatible process carried out on SOI wafers, we have built high-performance torsional microscanners having vertically offset interdigitated-comb actuators. Our microscanner-fabrication process requires three photolithography masks: two to form the front-side microscanner structures and a third to define the backside openings. Both moving and fixed combs are fabricated in the same device layer (30 mum in thickness), and the offset combs are created by reducing the thickness of the fixed combs, but not that of the moving combs. Our process begins by removing the 1-mum thick thermal oxide selectively to open rectangular windows at locations where the fixed combs are to be defined. In the following step, both fixed- and moving-comb sets are defined simultaneously with a single photolithography mask; this is followed by deep-reactive ion etching (DRIE). We then perform a tuned-etch in the DRIE-etcher to obtain the desired vertical thickness for the fixed combs without affecting the moving combs. The minimum gap between comb fingers can be as small as twice the alignment accuracy of the photolithography process, which is les0.4 mum for state-of-the-art photolithography steppers. We consider these microscanners as especially well adapted for applications to refractive laser surgery of ocular corneas where small spot size and high scan speeds are important assets

Conformal Liquid-Metal Electrodes for Flexible Graphene Device Interconnects

A novel integration technique is demonstrated that combines 2-D graphene with galinstan (eutectic gallium-based alloy) into flexible, compact, and durable devices. This unique combination enables the next-generation electronic devices with miniaturized microfluidic capabilities. Robust performance is exhibited across a wide range of flexure with less than 5.5% resistance change when subjected to repeated deformations as small as a 4-mm radius of curvature. To fully integrate both graphene and liquid metal in a microfluidics platform, robust interconnects are realized for a variety of flexible electronics applications.

Rapid Fabrication of Graphene Field-Effect Transistors with Liquid-metal Interconnects and Electrolytic Gate Dielectric Made of Honey

Historically, graphene-based transistor fabrication has been time-consuming due to the high demand for carefully controlled Raman spectroscopy, physical vapor deposition, and lift-off processes. For the first time in a three-terminal graphene field-effect transistor embodiment, we introduce a rapid fabrication technique that implements non-toxic eutectic liquid-metal Galinstan interconnects and an electrolytic gate dielectric comprised of honey. The goal is to minimize cost and turnaround time between fabrication runs; thereby, allowing researchers to focus on the characterization of graphene phenomena that drives innovation rather than a lengthy device fabrication process that hinders it. We demonstrate characteristic Dirac peaks for a single-gate graphene field-effect transistor embodiment that exhibits hole and electron mobilities of 213 ± 15 and 166 ± 5 cm2/V·s respectively. We discuss how our methods can be used for the rapid determination of graphene quality and can complement Raman Spectroscopy techniques. Lastly, we explore a PN junction embodiment which further validates that our fabrication techniques can rapidly adapt to alternative device architectures and greatly broaden the research applicability.

Rapid monodisperse microencapsulation of single cells

A microfluidic device was designed having the ability to continuously produce monodisperse microcapsules with controlled cell loading. The design included stages of inertial focusing, droplet generation, and photopolymerization. Prototype microfluidic devices were fabricated in polydimethylsiloxane (PDMS) to demonstrate each stage using poly(ethylene-glycol)-diacrylate (PEGDA) as the encapsulating material and oil as the droplet-containing medium, creating a water-in-oil emulsion. 10.3-µm-diameter fluorescent polystyrene beads were used as cell simulants. In the first stage, inertial focusing was demonstrated using a straight-channel configuration. In the second stage, droplets with a 60±5µm diameter were generated. In the third stage, successful encapsulation of the beads in hydrogel droplets was verified. This technology can significantly impact a wide research area ranging from cellular therapeutics to single-cell manipulation.

Force Transducer Through Total Internal Reflection and Frustrated Total Internal Reflection for a Three-Axis Anemometer

This paper introduces a method for measuring forces applied in a normal direction to the device using frustrated total internal reflection (FTIR) and infrared technology. Using FTIR for measuring force is not a new concept, but the past systems have used this principle by changing the material at the surface to change the refractive index at the point of contact. The design we propose causes a physical deformation to the waveguide, which causes changes in the output of the transducer. The transducer is designed to be implemented in a low cost three-axis anemometer for use in high-spatial resolution data gathering for wind generation stabilization. Our data supports the design of our transducer as it shows a correlation between the force and deformation of the upper surface of the waveguide and the output of the infrared phototransistor. The final section of the paper suggests a new design for a three-axis anemometer using the newly developed transducer.